Immunodetection of Glycosylated NT-proBNP Circulating in Human Blood

Seferian, Karina R.; Tamm, Natalia N.; Semenov, Alexander G.; Tolstaya, Anastasia A.; Koshkina, Ekaterina V.; Krasnoselsky, Mihail I.; Postnikov, Alexander B.; Serebryanaya, Daria V.; Apple, Fred S.; Murakami, MaryAnn M.; Katrukha, Alexey G.

doi:10.1373/clinchem.2007.100040

Cited by 101 publications

(127 citation statements)

References 9 publications

(20 reference statements)

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“…ProBNP in nonprocessed form is found in healthy individuals and patients with HF (18 ). ProBNP is posttranslationally modified in patients with HF by O-glycosylation at several threonine and serine residues within the N-terminal region (amino acid residues 1-76), but not within the BNP-portion of proBNP (amino acid residues 77-108) (19 ). It appears that NTproBNP is glycosylated in the central region (amino acid residues 28 -56), while the C-terminus region of the molecule (amino acid residues 61-76) is not posttranslationally modified (19 ).…”

Section: Bnpmentioning

confidence: 99%

“…ProBNP is posttranslationally modified in patients with HF by O-glycosylation at several threonine and serine residues within the N-terminal region (amino acid residues 1-76), but not within the BNP-portion of proBNP (amino acid residues 77-108) (19 ). It appears that NTproBNP is glycosylated in the central region (amino acid residues 28 -56), while the C-terminus region of the molecule (amino acid residues 61-76) is not posttranslationally modified (19 ). ProBNP, however, is glycosylated both in the central region and in the region located close to the cleavage site, specifically at amino acid residues 63-76.…”

Section: Bnpmentioning

confidence: 99%

“…Clinicians should be aware that these detection platforms underestimate the concentration of circulating biomarker considerably. Some studies suggest that the underestimation might be up to 10-fold (19,35 ). Some recommend that future NT-proBNP platforms use deglycosylation of blood samples before assay.…”

Section: Nt-probnp Assaysmentioning

confidence: 99%

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Natriuretic Peptides and Analytical Barriers

Vasile

Jaffe

2017

Clinical Chemistry

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BACKGROUND:The natriuretic peptide system is an endocrine, autocrine and paracrine system that plays an important role in the maintenance of cardiovascular homeostasis. Biomarkers based on these peptides are important diagnostic and prognostic tools for myocardial function.CONTENT: Although natriuretic peptides were discovered more than 2 decades ago, their intricate and complex biology is associated with important questions not yet elucidated. The diversity of circulating forms of natriuretic peptides, the distinct expression of these forms in particular patients, and the heterogeneity of heart failure forms, along with specific assay-related and preanalytic issues, cause assays to be poorly harmonized.

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Section: Bnpmentioning

confidence: 99%

Section: Bnpmentioning

confidence: 99%

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Natriuretic Peptides and Analytical Barriers

Vasile

Jaffe

2017

Clinical Chemistry

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“…Moreover, a recent study [34] suggested that the commercial immunoassays, commonly used for NTproBNP assay, employ non-glycosylated calibrator materials and mostly antibodies directed against epitopes with potential O-glycosylation site occupancy. Because the most part of circulating inactive peptides related to NT-proBNP and proBNP are O-glycosylated [7,18,35], these immunoassays cannot measure some glycosylated peptides [34,36]. Moreover, the commercially available immunoassays for NT-proBNP are interfered by the intact peptide proBNP (especially non-glycosylated peptide) [36] and also by some other shorter peptides derived from the proteolytic degradation of this pro-hormone [1] (Figure 2).…”

Section: Groupmentioning

confidence: 99%

“…In addition to the peptide hormone BNP and the inactive peptide NT-proBNP, a huge numbers of other circulating peptides derived from the pro-hormone proBNP can be identified by chromatographic procedures in human plasma, including the intact and glycosylated forms of proBNP itself [29][30][31][32][33]38] (Figure 2). Furthermore, the active hormone BNP may be produced even in vivo from the circulating intact precursor proBNP through enzymatic cleavage by some plasma proteases (such as corin) [35,36,39] (Figure 2). Indeed, a recent study, using an in vivo experimental rat model, demonstrated that the split of proBNP into BNP and NT-proBNP can actually occur in circulation [40].…”

Section: Quality Specifications For An Accurate Bnp Assaymentioning

confidence: 99%

New issues on measurement of B-type natriuretic peptides

Clerico

Zaninotto

Passino

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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Abstract:The measurement of the active hormone of B-type natriuretic peptide (BNP) system actually has several analytical limitations and difficulties in clinical interpretations compared to that of inactive peptide N-terminal proBNP (NT-proBNP) because of the different biochemical and pathophysiological characteristics of two peptides and quality specifications of commercial immunoassay methods used for their measurement. Because of the better analytical characteristics of NT-proBNP immunoassays and the easier pathophysiological and clinical interpretations of variations of NT-proBNP levels in patients with heart failure (HF), some authors claimed to measure the inactive peptide NT-proBNP instead of the active hormone BNP for management of HF patients. The measurement of the active peptide hormone BNP gives different, but complementary, pathophysiological and clinical information compared to inactive NT-proBNP. In particular, the setup of new more sensitive and specific assays for the biologically active peptide BNP 1-32 should give better accurate information on circulating natriuretic activity. In conclusion, at present time, clinicians should accurately consider both the clinical setting of patients and the analytical characteristics of BNP and NT-proBNP immunoassays in order to correctly interpret the variations of natriuretic peptides measured by commercially available laboratory methods, especially in patients treated with the new drug class of angiotensin receptor-neprilysin inhibitors.

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NT‐proBNP/BNP ratio for prognostication in European Caucasian patients enrolled in a heart failure prevention programme

et al. 2021

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Aims Guidelines support the role of B‐type natriuretic peptide (BNP) and amino‐terminal pro‐BNP (NT‐proBNP) for risk stratification of patients in programmes to prevent heart failure (HF). Although biologically formed in a 1:1 ratio, the ratio of NT‐proBNP to BNP exhibits wide inter‐individual variability. A report on an Asian population suggests that molar NT‐proBNP/BNP ratio is associated with incident HF. This study aims to determine whether routine, simultaneous evaluation of both BNP and NT‐proBNP is warranted in a European, Caucasian population. Methods and Results We determined BNP and NT‐proBNP levels for 782 Stage A/B HF patients in the STOP‐HF programme. The clinical, echocardiographic, and biochemical associates of molar NT‐proBNP/BNP ratio were analysed. The primary endpoint was the adjusted association of baseline molar NT‐proBNP/BNP ratio with new‐onset HF and/or progression of left ventricular dysfunction (LVD). We estimated the C‐statistic, integrated discrimination improvement, and the category‐free net reclassification improvement metric for the addition of molar NT‐proBNP/BNP ratio to adjusted models. The median age was 66.6 years [interquartile range (IQR) 59.5–73.1], 371 (47.4%) were female, and median molar NT‐proBNP/BNP ratio was 1.91 (IQR 1.37–2.93). Estimated glomerular filtration rate, systolic blood pressure, left ventricular mass index, and heart rate were associated with NT‐proBNP/BNP ratio in a linear regression model (all P < 0.05). Over a median follow‐up period of 5 years (IQR 3.4–6.8), 247 (31.5%) patients developed HF or progression of LVD. Log‐transformed NT‐proBNP/BNP ratio is inversely associated with HF and LVD risk when adjusted for age, gender, diabetes, hypertension, vascular disease, obesity, heart rate, number of years of follow‐up, estimated glomerular filtration rate, and baseline NT‐proBNP (odds ratio 0.71, 95% confidence interval 0.55–0.91; P = 0.008). However, molar NT‐proBNP/BNP ratio did not increase the C‐statistic (Δ −0.01) and net reclassification improvement (0.0035) for prediction of HF and LVD compared with NT‐proBNP or BNP alone. Substitution of NT‐proBNP for BNP in the multivariable model eliminated the association with HF and LVD risk. Conclusions This study characterized, for the first time in a Caucasian Stage A/B HF population, the relationship between NT‐proBNP/BNP ratio and biological factors and demonstrated an inverse relationship with the future development of HF and LVD. However, this study does not support routine simultaneous BNP and NT‐proBNP measurement in HF prevention programmes amongst European, Caucasian patients.

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Immunodetection of Glycosylated NT-proBNP Circulating in Human Blood

Cited by 101 publications

References 9 publications

Natriuretic Peptides and Analytical Barriers

Natriuretic Peptides and Analytical Barriers

New issues on measurement of B-type natriuretic peptides

NT‐proBNP/BNP ratio for prognostication in European Caucasian patients enrolled in a heart failure prevention programme

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